Pathogenic Bacterial Biofilms Research Articles

Enterococcus mundtii A2 biofilm and its anti-adherence potential against pathogenic microorganisms on stainless steel 316L.

Pathogenic bacterial biofilms present significant challenges, particularly in food safety and material deterioration. Therefore, using Enterococcus mundtii A2, known for its antagonistic activity against pathogen adhesion, could serve as a novel strategy to reduce pathogenic colonization within the food sector. This study aimed to investigate the biofilm-forming ability of E. mundtii A2, isolated from camel milk, on two widely used stainless steels within the agri-food domain and to assess its anti-adhesive properties against various pathogens, especially on stainless steel 316L. Additionally, investigations into auto-aggregation and co-aggregation were also conducted. Plate count methodologies revealed increased biofilm formation by E. mundtii A2 on 316L, followed by 304L. Scanning electron microscopy (SEM) analysis revealed a dense yet thin biofilm layer, playing a critical role in reducing the adhesion of L. monocytogenes CECT 4032 and Staphylococcus aureus CECT 976, with a significant reduction of ≈ 2 Log CFU/cm2. However, Gram-negative strains, P. aeruginosa ATCC 27853 and E. coli ATCC 25922, exhibit modest adhesion reduction (~ 0.7 Log CFU/cm2). The findings demonstrate the potential of applying E. mundtii A2 biofilms as an effective strategy to reduce the adhesion and propagation of potentially pathogenic bacterial species on stainless steel 316L.

Antibiofilm potential of biosurfactant produced by Bacillus aerius against pathogen bacteria

Biosurfactants (BS) derived from various microbes forms an alternative to chemical surfactants, which have many applications in food, petroleum, cosmetics, pharmaceutical industries. The present work aims to explore and identify new molecules and methods for the treatment of pathogenic bacterial biofilms. The findings of screening tests demonstrate Bacillus aerius ability to synthesize a surfactant with an emulsification index (EI24%) of 72.2% and a critical micellar concentration (CMC) of 60 mg/L. This BS effectively reduces surface tension, leading to a significant decrease from an initial value of 72 mN/m to 26 mN/m. This BS have been preliminarily characterized, Molecules identified by gas chromatography-mass spectrometry (GC-MS) have a high affinity with P. aeruginosa target proteins notably: AHL Synthase LasI (1RO5), virulence factor LasA (3IT7) and transcription protein LasR (6MNV). Similarly, the effect of BS on P. aeruginosa biofilm formation, in vitro, showed strong inhibition. Therefore, our study suggests that the crude biosurfactant from B. aerius is an effective anti-Quorum sensing/antibiofilm and antibacterial agent, warranting further investigation to explore its therapeutic applications.

Synergistic D-Amino Acids Based Antimicrobial Cocktails Formulated via High-Throughput Screening and Machine Learning.

Antimicrobial resistance (AMR) from pathogenic bacterial biofilms has become a global health issue while developing novel antimicrobials is inefficient and costly. Combining existing multiple drugs with enhanced efficacy and/or reduced toxicity may be a promising approach to treat AMR. D-amino acids mixtures coupled with antibiotics can provide new therapies for drug-resistance infection with reduced toxicity by lower drug dosage requirements. However, iterative trial-and-error experiments are not tenable to prioritize credible drug formulations, owing to the extremely large number of possible combinations. Herein, a new avenue is provide to accelerate the exploration of desirable antimicrobial formulations via high-throughput screening and machine learning optimization. Such an intelligent method can navigate the large search space and rapidly identify the D-amino acid mixtures with the highest anti-biofilm efficiency and also the synergisms between D-amino acid mixtures and antibiotics. The optimized drug cocktails exhibit high antimicrobial efficacy while remaining non-toxic, which is demonstrated not only from in vitro assessments but also the first in vivo study using a lung infection mouse model.

Pathogenic Biofilm Removal Potential of Wild-Type Lacticaseibacillus rhamnosus Strains.

The emergence of antimicrobial resistance remains one of the greatest public health concerns. Biofilm formation has been postulated as a mechanism of microbial pathogens to resist antimicrobial agents. Lactic Acid Bacteria (LAB) and their metabolites have been proposed to combat bacterial biofilms due to their antimicrobial activity. In this vein, the aim of the present study was to investigate the biofilm removal potential of cell-free supernatants (CFSs) of five wild-type Lacticaseibacillus rhamnosus strains, isolated from Greek natural products, in comparison to the commercially available L. rhamnosus GG strain, against biofilms formed by common foodborne pathogens (Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus). The biofilm removal activity of LAB was assessed on a two-day-old mature biofilm using a microtiter plate-based procedure. Both non-neutralized and neutralized CFSs removed biofilms in a concentration-dependent manner. The biofilm removal activity of the non-neutralized CFSs was significantly higher compared to the neutralized CFSs, as expected, with ranges of 60-89% and 30-80%, respectively. The biofilm removal efficiency of L. rhamnosus OLXAL-3 was significantly higher among the wild-type L. rhamnosus strains tested (20-100% v/v). In conclusion, our results suggest the great potential of the application of wild-type L. rhamnosus strain' CFSs as effective natural agents against pathogenic bacterial biofilms.

IN VITRO ANTIBACTERIAL AND ANTIBIOFILM ACTIVITIES OF ULTRAFILTRATED-BROMELAIN AGAINST DENTAL CARIES PATHOGENS

Dental plaque on tooth surfaces significantly contributes to dental caries leading to acidic demineralization of the tooth enamel and dentin. This is mainly caused by the formation of pathogenic bacterial biofilm. Dental caries affects approximately 3.5 million people around the world. Compared to synthetic anticariogenic agents such as chlorohexidine, plant-based compounds were found to have fewer side effects and higher economic value. Pineapple (Ananas comosus) is one of the largely commercialized plants in Malaysia with beneficial attributes such as its Bromelain enzyme. This study aimed to purify Bromelain enzyme from MD2 pineapple core and to evaluate their antibacterial properties against dental caries-associate pathogens in vitro. This study evaluated the effect of Bromelain enzyme isolated from MD2 pineapple core using 50% Ammonium Sulphate precipitation incorporated with centrifugal ultrafiltration against Streptococcus mutans, Staphylococcus aureus, Lactobacillus acidophilus, and Lactobacillus casei. Bromelain enzyme showed effectivity of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) for all cariogenic organisms. Ultrafiltrate Bromelain (UFB) enzyme had significant antibacterial activity against S.mutans with a MIC value of 250 μg/ml and complete susceptibility at an MBC value of 1000 μg/ml. Biofilm inhibition against S.mutans increased from 45.98% to 57.48% with ultrafiltration. A 3.25 purification fold increase was observed in the ultrafiltrate sample. In conclusion, the ultrafiltration technique is efficient in purifying Bromelain enzyme and effectively inhibits S. mutans biofilm formation and thus possesses a potential inhibitory effect on dental caries in vitro.

In vitro biofilm inhibition efficacy of Aerva lanata flower extract against Gram negative and Gram-positive biofilm forming bacteria and toxicity analysis using Artemia salina

A biofilm consists of Gram positive and Gram-negative bacteria enclosed in a matrix. Industrial biofouling is caused by biofilms, which can exhibit antimicrobial resistance during infections. Many biofilm studies find that nearly all biofilm communities consist of Gram positive and Gram-negative bacteria. It is therefore necessary to better understand the conserved themes in biofilm formation to develop therapeutics based on biofilm formation. Plant extracts can effectively combat pathogenic bacterial biofilms. This study evaluated the antibacterial and antibiofilm activity of Aerva lanata flower extract against Staphylococcus aureus and Pseudomonas aeruginosa. Methanol extract of dried A. lanata flower was tested against S. aureus and P. aeruginosa to determine the antibacterial activity (10, 25, 50, 75, 100 μg/mL) resulted in a maximum of 0.5–1 log reduction and 2 log reduction in comparison to the control or untreated bacterial cells respectively. A. lanata showed maximum biofilm inhibition up to 1.5-fold and 1-fold against P. aeruginosa and S. aureus. Light microscopic analysis of biofilm treated with A. lanata extract showed efficient distortion of the biofilm matrix. Further, the in vivo analysis of A. lanata in the Artemia salina brine shrimp model showed >50% survival and thus proving the efficacy of A. lanata extract in rescuing the brine shrimps against P. aeruginosa and S. aureus infection.

Complexation of Terpenes for the Production of New Antimicrobial and Antibiofilm Molecules and Their Encapsulation in Order to Improve Their Activities

Microbiological risk associated with abiotic surfaces is one of the most important issues worldwide. Surface contaminations by pathogenic bacterial biofilms or adherent cells affect a number of sectors, including medical services, food industries, human services, and the environment. There is a need to synthesize or to set up novel biosource-based antimicrobials. Terpenes such as limonene carvacrol are usually found in essential oils and have potent antimicrobial activities. However, the direct use of these molecules is often inefficient due to their low water solubility, loss of volatile compounds, thermal degradation, oxidation, and toxicity. The organic synthesis of stable metal complexes based on terpene ligands seems to be a promising issue, since it can allow for and promote the use of terpenes and challenge the drawbacks of these molecules. Spray drying could be the most suitable method for encapsulating metal complexes based on terpene ligands to protect and enhance their activity against bacterial biofilms. The goal of this review is to discuss the microbiological risk associated with pathogenic bacterial biofilm and the organic synthesis of novel antimicrobial complexes based on terpene ligands. In addition, this review explores how to improve their bioactivities and characteristics using a formulation based on encapsulation.

Green Synthesis of MOF-Mediated pH-Sensitive Nanomaterial AgNPs@ZIF-8 and Its Application in Improving the Antibacterial Performance of AgNPs.

Herein, an emerging drug delivery system was constructed based on zeolite imidazole backbone (ZIF-8) to improve antibacterial defects of nanosilver (AgNPs), such as easily precipitated and highly cytotoxic. The homogeneous dispersion of AgNPs on ZIF-8 was confirmed by UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM. The appropriate AgNPs loading ratio on ZIF-8 was screened through the cell and antibacterial experiments based on biosafety and antibacterial performance. The optimal environment for AgNPs@ZIF-8 to exert antibacterial performance was probed in the context of bacterial communities under different acid-base conditions. The potential mechanism of AgNPs@ZIF-8 to inhibit the common clinical strains was investigated by observing the biofilm metabolic activity and the level of reactive oxygen species (ROS) in bacteria. The successful piggybacking of AgNPs by ZIF-8 was confirmed using UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM characterization methods. Based on the bacterial growth curve (0-24 hours), the antibacterial ability of AgNPs@ZIF-8 was found to be superior to AgNPs. When the mass ratio of ZIF-8 and AgNPs was 1:0.25, the selection of AgNPs@ZIF-8 was based on its superior antimicrobial efficacy and enhanced biocompatibility. Notably, under weakly acidic bacterial microenvironments (pH=6.4), AgNPs@ZIF-8 demonstrated a more satisfactory antibacterial effect. In addition, experiments on biofilms showed that concentrations of AgNPs@ZIF-8 exceeding 1×MIC resulted in more than 50% biofilm removal. The nanomedicine was found to increase ROS levels upon detecting the ROS concentration in bacteria. Novel nanocomposites consisting of low cytotoxicity drug carrier ZIF-8 loaded with AgNPs exhibited enhanced antimicrobial effects compared to AgNPs alone. The pH-responsive nano drug delivery system, AgNPs@ZIF-8, exhibited superior antimicrobial activity in a mildly acidic environment. Moreover, AgNPs@ZIF-8 effectively eradicated pathogenic bacterial biofilms and elevated the intracellular level of ROS.

Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms

Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic "nano-sword" with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.

Gene Expression Quantification from Pathogenic Bacterial Biofilms by Quantitative PCR.

Quantitative PCR (qPCR) is one of the most used techniques to quantify gene expression in bacterial biofilms due to its easiness, sensitivity, and robustness. However, several practical aspects need to be considered to obtain accurate and reliable results. Here, we describe a detailed and optimized protocol to quantify mRNA transcripts from bacterial biofilms using qPCR, including pieces of advice to improve RNA quality, which ultimately increases the accuracy, consistency, and relevance of gene expression data.

Yersinia enterocolitica-Derived Outer Membrane Vesicles Inhibit Initial Stage of Biofilm Formation.

Yersinia enterocolitica (Y. enterocolitica) is an important food-borne and zoonotic pathogen. It can form biofilm on the surface of food, increasing the risk to food safety. Generally, outer membrane vesicles (OMVs) are spherical nanostructures secreted by Gram-negative bacteria during growth. They play a role in biological processes because they contain biologically active molecules. Several studies have reported that OMVs secreted by various bacteria are associated with the formation of biofilms. However, the interactions between Y. enterocolitica OMVs and biofilm are unknown. This study aims to investigate the effect of Y. enterocolitica OMVs on biofilm formation. Firstly, OMVs were extracted from Y. enterocolitica Y1083, which has a strong biofilm-forming ability, at 15 °C, 28 °C and 37 °C and then characterized. The characterization results showed differences in the yield and protein content of three types of OMVs. Next, by co-culturing the OMVs with Y. enterocolitica, it was observed that the OMVs inhibited the initial stage of Y. enterocolitica biofilm formation but did not affect the growth of Y. enterocolitica. Furthermore, biofilm formation by Salmonella enteritidis and Staphylococcus aureus were also inhibited by OMVs. Subsequently, it was proved that lipopolysaccharides (LPS) in OMVs inhibited biofilm formation., The proteins, DNA or RNA in OMVs could not inhibit biofilm formation. Bacterial motility and the expression of the biofilm-related genes pgaABC, motB and flhBD were inhibited by LPS. LPS demonstrated good anti-biofilm activity against various bacteria. This study provides a new approach to the prevention and control of pathogenic bacterial biofilm.

Antibiofilm and enhanced antibiotic delivery by halloysite nanotubes architected dental implant against periodontitis

Dental implant failure remains a predominant problem; poor integration and biofilm formation are the major glitches. The surface modification of implant improves it antibiotic delivery performance and nanostructure incorporation facilitates the versatile behavior. Herein, we have prepared PCPP functionalized HNT and it encapsulated with AMO and MS. FTIR confirms the PCPP coating over the HNT by formation of new peaks at 1640 and 1580 cm−1. Higher stability of HNT nanocomposites was denoted by its zeta value – 45.24 mV. The maximum release of 58% (AMO) and 62% (MS) from the nanocomposites was achieved at the acidic pH. PCPP coated MS-HNT nanocomposites forms lumen size ranging from 15 to 20 nm with uniform surface morphology. Simultaneously, bioactive MS-AMO-PCPP-HNT was deposited on the Ti–6Al–4V screw implant via electrophoretic deposition. The coating of HNT nanocomposites on titanium surface provides 7.24 μm thickness and adhesive strength of 24.6 MPa. After EPD of MS-AMO-PCPP-HNT on Ti–6Al–4V screw, the surface is fully covered by adequate bonding, stable coating, biocompatible and long-lasting antibacterial efficacy. The potentiodynamic study in the SBF shows that the coating provided corrosion protection of the screw. The coated Ti–6Al–4V screw surface composition enhances the biomineralization, promote the cell adhesion, proliferation and promote the soft tissue healing. Compared to the HNT, PCPP-HNT nanocomposites induces the ALP production, increase the cell proliferation rate at 20 μg/mL. In flow cytometry, biocompatible HNT nanocomposites exhibited lesser dead cells of 0.56%. HNT nanocomposites inhibit the 96% (E.coli) and 97% (S. aureus) bacterial inhibition and the rate were higher compared to the AMO alone. Also reduction of 78% of Porphyromonas gingivalis biofilm biomass, the coating is powerfully active against the both pathogenic microbes and bacterial biofilm of peri-implant infection. The nano-architected coating of Ti–6Al–4V screw has great potential in dental implantology.

Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses.

Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.

Activatable iodinated BODIPYs for selective imaging and photodynamic disruption of amyloid structures in pathogenic bacterial biofilms

We report the application of two iodinated boron dipyrromethene (BODIPY) photocatalysts as theranostic compounds against pathogenic bacterial biofilms. These derivatives, which are activated through a polarity effect upon binding, have exquisite selectivity towards amyloids in the biofilm extracellular matrix (ECM). This property can be exploited in fluorescence microscopy to stain the ECM of uropathogenic bacterial biofilms, displaying a superior selectivity compared to Thioflavin T, the gold standard for amyloid detection. Moreover, we show that the ability of these compounds to photosensitize reactive oxygen species upon binding can be used to weaken the mechanical barrier of the ECM and restore the activity of conventional antimicrobial agents, whose effect is strongly limited in intact biofilms. The combination of activatable near-infrared fluorescence and photo-oxygenation properties of these compounds upon binding to amyloid structures provides a powerful theranostic tool for simultaneous detection and treatment of pathogenic biofilm infections.

The Role of Lactic Acid in the Management of Bacterial Vaginosis: A Systematic Literature Review

Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a considerable challenge given that about 60% of women experience BV relapse within six months after initial treatment. In addition, clear guidelines on the treatment of asymptomatic BV during pregnancy or for BV mixed infections are still missing. Lactic acid has been put forward as a potential treatment or for prophylaxis of BV due to its ability to restore the imbalance of the vaginal microbiota and to promote the disruption of vaginal pathogenic bacterial biofilms, which might trigger BV recurrence. This review evaluates the clinical evidence regarding the efficacy and prophylactic potential of lactic acid in BV through a systematic literature search. In addition, a treatment regimen consisting of lactic acid as a standalone treatment or in combination with current recommended therapies for practice is suggested based on these findings and stratified according to BV severity, pregnancy status, and coincidence with vulvovaginal candidosis (VVC) or trichomoniasis.

Multi-Strain and -Species Investigation of Volatile Metabolites Emitted from Planktonic and Biofilm Candida Cultures.

Candida parapsiliosis is a prevalent neonatal pathogen that attains its virulence through its strain-specific ability to form biofilms. The use of volatilomics, the profiling of volatile metabolites from microbes is a non-invasive, simple way to identify and classify microbes; it has shown great potential for pathogen identification. Although C. parapsiliosis is one of the most common clinical fungal pathogens, its volatilome has never been characterised. In this study, planktonic volatilomes of ten clinical strains of C. parapsilosis were analysed, along with a single strain of Candida albicans. Headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry were employed to analyse the samples. Species-, strain-, and media- influences on the fungal volatilomes were investigated. Twenty-four unique metabolites from the examined Candida spp. (22 from C. albicans; 18 from C. parapsilosis) were included in this study. Chemical classes detected across the samples included alcohols, fatty acid esters, acetates, thiols, sesquiterpenes, and nitrogen-containing compounds. C. albicans volatilomes were most clearly discriminated from C. parapsilosis based on the detection of unique sesquiterpene compounds. The effect of biofilm formation on the C. parapsilosis volatilomes was investigated for the first time by comparing volatilomes of a biofilm-positive strain and a biofilm-negative strain over time (0–48 h) using a novel sampling approach. Volatilomic shifts in the profiles of alcohols, ketones, acids, and acetates were observed specifically in the biofilm-forming samples and attributed to biofilm maturation. This study highlights species-specificity of Candida volatilomes, and also marks the clinical potential for volatilomics for non-invasively detecting fungal pathogens. Additionally, the range of biofilm-specificity across microbial volatilomes is potentially far-reaching, and therefore characterising these volatilomic changes in pathogenic fungal and bacterial biofilms could lead to novel opportunities for detecting severe infections early.

Astodrimer sodium and bacterial vaginosis: a mini review

Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women’s physical, emotional, sexual and social lives, as well as being linked to a number of gynaecological and obstetrical complications and adverse pregnancy outcomes. Antibiotics, such as metronidazole or clindamycin, are recommended as first-line treatment for BV, but may be associated with antibiotic resistance, high rates of recurrence and poor patient treatment satisfaction. Astodrimer sodium gel is a novel, non-antibiotic treatment for BV that is not systemically absorbed. It prevents pathogenic bacteria from adhering to the vaginal wall, and disrupts and inhibits the formation of pathogenic bacterial biofilms. Clinical cure rates of 50–57% were observed in patients with BV treated with astodrimer sodium compared with 17–21% treated with placebo (p < 0.001) in Phase 3 trials. In a separate Phase 3 trial, recurrence of BV occurred in 44% of patients treated with astodrimer sodium compared with 54% of patients who received placebo (p = 0.015). Astodrimer sodium is well tolerated, with vulvovaginal candidosis being the only treatment-related adverse event reported to occur more often than with placebo. The availability of astodrimer sodium, a well-tolerated, convenient, non-antibiotic treatment for BV, represents significant progress in the treatment of this burdensome condition.

NIR responsive nitric oxide nanogenerator for enhanced biofilm eradication and inflammation immunotherapy against periodontal diseases

Periodontal disease is one of the most common oral infectious diseases and closely related to many systemic diseases which is in urgent need of novel and effective drugs. In particular, the problems of deep lesion location and synchronization of antibacterial and anti-inflammatory needs to be addressed. Herein, near infrared (NIR) light triggered nanoplatform with antibacterial and anti-inflammatory dual-functions by antibacterial photodynamic therapy (aPDT), photothermal therapy (PTT) and gas therapy was realized by loading S-nitrosothiols (SNO) and ICG into mesoporous silica-coated gold nanorods. Using a single 808 nm NIR light, the excellent antibacterial efficacy can be achieved not only by aPDT-induced bacteria killing but also by PTT-triggered biofilm dispersal. Furthermore, SNO molecules would also be thermally activated to release nitric oxide (NO) gas molecules at the site of periodontal disease, exerting inflammation inhibition by suppressing the assembly of pro-inflammatory factors and NLRP3 inflammasome. Additionally, such nanoplatform could validly combat pathogenic bacterial biofilm, and modulate the inflammatory immunity, leading to favorable therapeutics on animal models with periodontal diseases. Hence, this design provides an effective solution to solve the problems of deep tissue treatment along with simultaneously antibacterial/anti-inflammatory capabilities, which provides a bright prospect for clinical treatment of periodontal diseases, even extended to other refractory infections in deep sites.

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review.

Bacterial biofilms formed by pathogens are known to be hundreds of times more resistant to antimicrobial agents than planktonic cells, making it extremely difficult to cure biofilm-based infections despite the use of antibiotics, which poses a serious threat to human health. Therefore, there is an urgent need to develop promising alternative antimicrobial therapies to reduce the burden of drug-resistant bacterial infections caused by biofilms. As natural enemies of bacteria, bacteriophages (phages) have the advantages of high specificity, safety and non-toxicity, and possess great potential in the defense and removal of pathogenic bacterial biofilms, which are considered to be alternatives to treat bacterial diseases. This work mainly reviews the composition, structure and formation process of bacterial biofilms, briefly discusses the interaction between phages and biofilms, and summarizes several strategies based on phages and their derivatives against biofilms and drug-resistant bacterial infections caused by biofilms, serving the purpose of developing novel, safe and effective treatment methods against biofilm-based infections and promoting the application of phages in maintaining human health.

A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection.

Multimodal synergistic bactericidal agents display great potential for fighting biofilm infections. However, the rational design of biofilm microenvironment (BME)-activatable therapeutic agents with excellent specificities, effective eradications and minimal side effects remains a great challenge. Herein, we show a BME-responsive one-for-all bactericidal nanoplatform consisting of Fe3+-doped polydopamine (Fe/PDA)-capped ZnO nanoparticles with a successive assembly of methylene blue (MB) and poly(ethylene glycol) (PEG). In an acidic BME (pH 5.5), the constructed nanoagent (ZnPMp) can realize the co-delivery of dual metal ions (Zn2+ and Fe3+) and MB, and the latter shows an activated photodynamic antibacterial activity when irradiated with 635 nm laser. Zn2+ produced from acid-sensitive dissolution of ZnO is an effective chemical antibacterial agent. Additionally, the released Fe3+ is reduced to Fe2+ by glutathione (GSH) overexpressed in the BME to generate Fe2+/Fe3+ redox couples, which exhibit Fenton catalytic activity to convert endogenous H2O2 to hydroxyl radicals (˙OH) for chemodynamic sterilization and GSH depletion ability to improve ˙OH-induced oxidative damage. Interestingly, the hyperthermia caused by the Fe/PDA layer assisted with 808 nm laser can damage directly bacterial cells, accelerate the release of Zn2+, Fe3+and MB, and promote the catalytic activity of Fe2+/Fe3+ redox couples for photothermal-augmented multimodal antibiofilm therapy. With the help of dual lasers, ZnPMp displays the broad-spectrum antibacterial effect, inhibits effectively the formation of biofilms, and more importantly eliminates bacteria deep in mature biofilms. In addition, ZnPMp can be used to treat biofilm-related infections in vivo with excellent therapeutic performance and minimal toxicity. Overall, the developed ZnPMp may serve as a potential nano-antibacterial agent for intensive anti-infective therapy.